This proposed research considers the forces acting on natural populations. The aim is to continue and extend theoretical, computational and data studies to investigate the inferences that can be made concerning these forces. The large and increasing body of data on genotypic frequencies in natural populations and studies on molecular evolutions raise a large number of important questions. Particular emphasis will be placed on developing models to aid in the understanding of these questions. In connection with the above the investigator aims to: 1. Determine the effects of different strengths of selection at individual loci on the final multi-locus equilibrium. 2. Develop multi-locus 'hitchhiking' models allowing a constant influx of new mutants with different selective values. 3. Develop multi-locus models with frequency dependent selection, as in host pathogen interactions. 4. Continue statistical analyses of population and family data on HLA (human histocompatibility system) associated diseases. 5. Develop two locus models which include HLA and non-HLA linked genetic factors predisposing individuals to disease. 6. Develop a model of molecular evolution where fitness is assumed to follow a distribution of values.